Papillomavirus are causative agents for several types of epithelial and mucosal diseases. Of particular concern is that certain strains of papillomavirus are associated with cervical and penile cancers (see, e.g., Iwasawa et al., J. Urol., 149, 59-63 (1993); Koutsky et al., N. Engl. J. Med., 327, 1272-78 (1992)). Considerable efforts, therefore, are underway to prevent the spread of this virus by developing a prophylactic vaccine and novel treatments for papillomavirus-induced lesions (see, e.g., Cason et al., Vaccine, 11, 603-11 (1993); Crawford, Cancer Surv., 16, 215-29 (1993)). Such efforts, however, have been hampered by the particular difficulties of working with papillomavirus in vitro. To complete its life cycle, papillomavirus requires its host cell to undergo a differentiation event. Currently, no in vitro culture system duplicates this state adequately to permit efficient papillomavirus growth in vitro.
Papillomaviruses are nonenveloped double-stranded DNA viruses about 55 nm in diameter with an approximately 8-kb genome in a nucleohistone core (Baker et al., Biophys J. 60, 1445-56 (1991)). The capsids include two viral proteins (L1 and L2) of about 55 kDa and 75 kDa, respectively (Larson et al., J. Virol., 61, 3596-3601 (1987)). L1 is the major capsid protein, and it is arranged in 72 pentameres within the capsid. In fact, L1 has the ability to self-assemble into virus-like particles (VLPs) upon production of the L1 protein in eukaryotic cells (see, e.g., Hagensee et al., J. Virol., 67, 315-22 (1993); Kirnbauer et al., J. Virol., 67, 6929-36 (1993)). The function and position of L2 within the virion are not clear, although the protein is assembled with L1 into VLPs when coexpressed in cells.
Because of the lack of suitable papillomavirus culture conditions, VLPs typically are used for in vitro studies of papillomavirus infection, as opposed to intact papillomavirus (see, e.g., Roden et al., J. Virol., 68, 7260-66 (1994); Volpers et al., J. Virol., 69, 3258-64 (1995)). Using VLPs, it is now thought that a putative cell receptor for papillomavirus is expressed across a wide range of cell types and is highly conserved between a diverse group of organisms (see, e.g., Muller et al., J Virol., 69, 948-54 (1995); Volpers et al., supra; Roden et al., supra). Currently, little is understood about papillomavirus infection, particularly the identity of a cell surface receptor recognizing papillomavirus.
In view of the foregoing problems, there exists a need for methods and reagents for treating or preventing papillomavirus infection.